LipidDB ID

LipidDB-9913-00700

Entry Name

UniProt Accession

P00517;

Theoretical PI

8.71

Molecular Weight

40619.71

Genbank Protein ID

CAA47627.1;

Genbank Nucleotide ID

X67154;

Protein Name

cAMP-dependent protein kinase catalytic subunit alpha

Protein Synonyms/Alias

PKA C-alpha; 2.7.11.11;

Gene Name

PRKACA

Gene Synonyms/Alias

Created Date

21-JUL-1986

Organism

Bos taurus (Bovine)

NCBI Taxa ID

9913

Reference

[1] Shoji S, Parmelee DC, Wade RD, Kumar S, Ericsson LH, Walsh KA, Neurath H, LongGL, Demaille JG, Fischer EH, Titani K. Complete amino acid sequence of thecatalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase.Proc Natl Acad Sci U S A. 1981 Feb;78(2):848-51.[PMID:6262777]
[2] Jedrzejewski PT, Girod A, Tholey A, König N, Thullner S, Kinzel V, Bossemeyer D. A conserved deamidation site at Asn 2 in the catalytic subunit of mammaliancAMP-dependent protein kinase detected by capillary LC-MS and tandem massspectrometry. Protein Sci. 1998 Feb;7(2):457-69.[PMID:9521123]

Functional Description

Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B- alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha- difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (By similarity).

Sequence Annotation

Domain: 44 298 Protein kinase.
Domain: 299 351 AGC-kinase C-terminal.
Nucleotide-binding: 50 58 ATP.
Nucleotide-binding: 122 128 ATP.
Nucleotide-binding: 169 172 ATP.
Active site: 167 167 Proton acceptor.
Binding site: 73 73 ATP.
Modified residue: 3 3 Deamidated asparagine; partial.
Modified residue: 11 11 Phosphoserine; by autocatalysis.
Modified residue: 49 49 Phosphothreonine.
Modified residue: 140 140 Phosphoserine.
Modified residue: 196 196 Phosphothreonine.
Modified residue: 198 198 Phosphothreonine; by PDPK1.
Modified residue: 202 202 Phosphothreonine.
Modified residue: 331 331 Phosphotyrosine.
Modified residue: 339 339 Phosphoserine.

Protein Length

351 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0031588; C:AMP-activated protein kinase complex; IEA:Ensembl
GO:0005813; C:centrosome; IEA:Ensembl
GO:0097546; C:ciliary base; IEA:Ensembl
GO:0005737; C:cytoplasm; ISS:AgBase
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0005739; C:mitochondrion; IEA:UniProtKB-KW
GO:0031594; C:neuromuscular junction; ISS:AgBase
GO:0005634; C:nucleus; IEA:UniProtKB-KW
GO:0005886; C:plasma membrane; IEA:UniProtKB-KW
GO:0097225; C:sperm midpiece; IEA:Ensembl
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0004691; F:cAMP-dependent protein kinase activity; ISS:UniProtKB
GO:0004672; F:protein kinase activity; ISS:AgBase
GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:Ensembl
GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl
GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl
GO:0001707; P:mesoderm formation; ISS:AgBase
GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl
GO:0001843; P:neural tube closure; IEA:Ensembl
GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl
GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl
GO:0071158; P:positive regulation of cell cycle arrest; IEA:Ensembl
GO:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl
GO:0046777; P:protein autophosphorylation; IEA:Ensembl
GO:0006468; P:protein phosphorylation; ISS:AgBase
GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl
GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl
GO:0070613; P:regulation of protein processing; IEA:Ensembl
GO:0050804; P:regulation of synaptic transmission; IEA:Ensembl
GO:2000810; P:regulation of tight junction assembly; IEA:Ensembl
GO:0048240; P:sperm capacitation; IEA:Ensembl

Interpro

InterPro; IPR000961; AGC-kinase_C
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR002290; Ser/Thr_dual-sp_kinase
InterPro; IPR008271; Ser/Thr_kinase_AS

Pfam

Pfam; PF00069; Pkinase;

SMART

SMART; SM00133; S_TK_X;
SMART; SM00220; S_TKc;

PROSITE

PROSITE; PS51285; AGC_KINASE_CTER;
PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00108; PROTEIN_KINASE_ST;

PRINTS